A binding mechanism in protein-nucleotide interactions: Implication for U1A RNA binding
A binding mechanism in protein-nucleotide interactions: Implication for U1A RNA binding
复制标题
DOI：
10.1073/pnas.0500888102
复制
发表时间：
2005-03-15
影响因子：
11.1
通讯作者：
Borrelli, KW
中科院分区：
文献类型：
--
作者：
Guallar, V;Borrelli, KW
我们提出了一个密切的电子视图的N-末端结构域的人类蛋白质U1 A的蛋白质-碱基界面。结合精确的混合量子力学/分子力学技术和蛋白质结构预测方法，我们提供了一个详细的电子结构描述的蛋白质-RNA堆积相互作用。我们的分析表明，蛋白质结构的进化优化了Asp-92和RNA碱基之间的相互作用。结果显示C-末端尾和Asp-92的直接偶联，提供了实验确定的C-末端结构域在RNA结合中的作用的直接合理化。在这里，我们提出了一种机制，其中蛋白质侧链，与离域电子π系统，协助核苷酸结合。结合机制涉及侧链与核苷酸碱基的短程相互作用和通过电子堆积基序的电子长程相互作用。在类似的蛋白质-RNA相互作用和各种蛋白质-ATP结合位点中观察到结合机制的结构基序。
We present a close electronic view of the protein-base interface for the N-terminal domain of the human protein U1A. Combining accurate mixed quantum mechanics/molecular mechanics techniques and protein structure prediction methods, we provide a detailed electronic structure description of the protein-RNA stacking interactions. Our analysis indicates the evolution of the protein structure optimizing the interaction between Asp-92 and the RNA bases. The results show a direct coupling of the C-terminal tail and Asp-92, providing a direct rationalization of the experimentally determined role of the C-terminal domain in RNA binding. Here, we propose a mechanism where a protein side chain, with a delocalized electronic pi system, assists in the nucleotide binding. The binding mechanism involves a short-range interaction of the side chain with the nucleotide base and an electronic long-range interaction through a sandwich-stacking motif. The structural motif of the binding mechanism is observed in similar protein-RNA interactions and in various protein-ATP-binding sites.